Synthesis of 2′,3′-Dideoxy-2′-Fluorokanamycin A

2′,3′-Dideoxy-2′-fluorokanamycin A (23) was prepared by condensation of 6-azido-4-0-benzoyl-2,3,6-trideoxy-2-fluoro-α-D-ribo-hexopyranosyl bromide (13) and a protected disaccharide (19). Methyl 4,6-0-benzylidene-3-deoxy-β-D-arabino-hexopyranoside (5) prepared from methyl 4,6-0-benzylidene-3-chloro-3-deoxy-β-D-allo-hexopyranoside (1) by oxidation with pyridinium chlorochromate followed by reduction with Na₂ S₂O₄ was fluorinated with the DAST reagent to give methyl 4,6-O-benzylidene-2,3-dideoxy-2-fluoro-β-D-ribo-hexopyranoside (7). Successive treatment of 7 with NBS, NaN₃ and SOBr₂ gave 13. The structure of the final product (23) was determined by the ¹H and ¹⁹F and shift-correlated 2D NMR spectra.     

A Conventient Synthesis of 3-Hydroxy-4-chromanone Using Iodobenzene Diacetate

A useful synthesis of 3-hydroxy-4-chromanone (6) is not currently available. Lead tetraacetate oxidation of 4-chromanone (4) yields the C(3) acetoxy derivative but this compound could not be deacetylated to 6.¹ Recently Donnelly and Maloney reported² that the Algar-Flynn-Oyamada reaction (H₂O₂/CH₃OH/NaOH), which is commonly used for the conversion of o-hydroxychalcones (1) into 3-hydroxyflavanone (2) and 3-hydroxyflavones (3), does not yield 6 when applied to o-hydroxya-crylophenone 1 (R = H). The authors found that under less basic conditions using K₂CO₃ some 6 is formed but the major product is catechol. These observations clearly indicate the necessity of developing a method for making 6. The present note describes a staightforward way of preparing 3-hydroxy-4-chromanone (6) in good yield.     

Reaktionen Mit Trimethylsilylhalogeniden an Derivaten Der Digitoxose

Abstract

Treatment of methyl 3,4-di-O-acyl-2,6-dideoxy-α-D-ribo-hexo-pyranoside 1 or 2 with trimethylsilyl halide leads to the formation of a complex mixture of α-D-ribo-hexopyranosyl halides 3 or 5 together with the educts 1 or 2 as well as their β-anomers 8 or 9. The bromides 3 and 5, suitable for glycosidations, are preferably obtained by reaction of the digitoxose acetate derivatives 6 and 7, respectively, which in turn are prepared from 1 and 2 by mild acetolysis. Further reaction of the halides 3 to 5 with trimethylsilyl halides gives rise to a quantitative formation of the 2,3,6-trideoxy-4-0-acyl-3-halo-α-D -arabino-hexopyranosyl halides 10 to 12. In another reaction sequence starting with the olivose triacetate 20 the formation of 10 via the halide 13 is demonstrated. Structural evidence for the halides 10 to 12 is given by ¹H NMR data as well as by analyses of their glycosides 14 to 19. The results support a mechanistic interpretation for the formation of 10 to 12 via a 3,4-acetoxonium ion as the key intermediate obtained from 3 by an S_Nfi and from 13 and S_N2i step. Final conversion into the terminal halodeoxy compounds 10 to 12 proceeds by and S_N2 reaction with the halide ion.     

Synthesis of (±)-cis-Calamenene;

Hydroboration of 4 furnishes a mixture of primary alcohols 5 and 6. The stereochemistry of the crystalline half ester 7 has been established by X-ray studies. While the oxidation of 5 with Jones reagent furnishes the aldehyde 9 in low yield due to the formation of the by product 3, oxidation with Moffatt reagent furnishes the aldehyde 9 in satisfactory yields. cis-Calamenene 1 has been prepared from 9.     

The Synthesis of Hydronaphthalenes from m-Toluic Acid via Cyclization of Thioacetal Monosulfoxides

We recently developed a convenient route to hexahydronaphthalenols such as 5 (R=CO₂CH₃ or CH₃) starting from m-toluic acid (1)¹. The key features of the route involved reduction-alkylation of the toluic acid to the dihydro derivative 2 ², subsequent deprotection and oxidation of the side chain primary alcohol, and acid-catalyzed cyclization of the resulting aldehyde 4. In the case of the dimethylnaphthalenols 5 (R=CH₃), conversion of the angular carboxylic function to the methyl group was effected prior to cyclization via reduction of the p-toluenesulfonic ester of the neopentyl alcohol 3 (R=CH₂OH) using lithium triethylborohydride³.     

Darstellung Der Isomeren 1,6-DI-O-Acetyl-3,4-Didesoxy-α, β-D-Glycero-Hex-3-Enopyrahos-2-Ulosen

Abstract

Prolonged treatment of tetra-O-acetyl-1, 5-anhydro-hex-1-enitols (“tetra-O-acetyl-hydroxy-glycals”) 3 and 5 with BF₃ in CH₂Cl₂ at RT lead to anomeric mixtures of the title compounds 2 and 4a, the α-anomer 4a dominating. Reaction of 5 gave the higher yields of 4a (71%) and 2 (12%), the results being accounted mechanistic grounds. The same reaction performed in an aromatic solvent, like toluene, gave rise to competing C-alkylation., The ortho and para-tolyl derivatives 6 and 7, also with enone structure, were isolated in a combined maximum yield of 40% from 5. β-Enone 2 was also prepared in moderate yield by thermolysis of β-d-glucopyranose pentaacetate (1). In this case no α-anomer 4a was detected.     

Synthesis of the Oligosaccharide Moieties of Musettamycin,Marcellomycin and Aclacinomycin A,Antitumor Antibiotics

Abstract

Condensation of benzyl 2,3,6-trideoxy-3-trifluoroacetamido-α-L-lyxo-hexopyranoside (5) with 4-O-acetyl-3-O-benzyl-2,6-dideoxy-α-L-lyxo-hexopyranosyl bromide (10) carried out under Koenigs-Knorr conditions gave 12. Total deprotection of 12 and N-dimethylation at C-3 led to 17 while selective removal of the 4-O-acetyl group led to 13, a synthetic intermediate for preparing 24 and 33. Condensation of 13 with di-O-acetyl-L-fucal (18) or 4-O-acetyl-L-amicetal (25) in the presence of N-iodosuccinimide followed by hydrogenolysis of the C-2-I bond gave 20 and 27 respectively. The trisaccharide 24 then was obtained from 20 by the same sequence of reactions used to convert 12 into 17. After deacetylation and oxidation, this set of reactions also transformed 27 into 33.     

Synthesis of O-α-L-Fucopyranosyl-(1→2)-O-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-D-glucopyranose. The H-Blood Group Specific Trisaccharide

Abstract

Different reaction conditions were investigated for the preparation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside (5). Compound 5 on reaction with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide afforded the 4-O-substituted 2-acetamido-2-deoxy-β-D-glucopyranosyl derivative which, on O-deacetylation, gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-glucopyranoside (8). The trimethylsilyl (Me₃Si) derivative of 8, on treatment with pyridineacetic anhydride-acetic acid for 2 days, gave the disaccharide derivative having an O-acetyl group selectively introduced at the primary position and Me₃Si groups at the secondary positions. The latter groups were readily cleaved by treatment with aqueous acetic acid in methanol to afford benzyl 2-acetamido-4-O-(6-O-acetyl-β-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside, which on isopropylidenation gave the desired, key intermediate benzyl 2-acetamido-4-O-(6-O-acetyl-3,4-O-isopropylidene-β-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside (12). Reaction of 12 with 2,3,4-tri-O-benzyl-α-L-fucopyranosyl bromide under catalysis by bromide ion afforded the trisaccharlde derivative from which the title trisaccharide was obtained by systematic removal of the protective groups. The structures of the final trisaccharide and of various intermediates were established by ¹H and ¹³C NMR spectroscopy.     

Stereoselective Synthesis of 3-C-Branched-Chain Sugars by Aldol Reaction of Furanos-3-Uloses with Acetone

Abstract

Aldol reaction of 1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-erythro-pentofuranos-3-ulose (1) with acetone in the presence of aqueous K₂CO₃ afforded 3-C-acetonyl-1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-ribofuranose(2). Similar reaction of 1,2:5, 6-di-o-isopropylidene- α-D-ribo-hexofuranos-3-ulose (3) afforded 3-C-acetonyl-1,2:5, 6-di-o-isopropylidene- α-D-allofuranose (4) and (1R, 3R, 7R, 8S, 10R)-perhydro-8-hydroxy-5,5,10-trimethyl-2,4,6,11,14-pentaoxatetracyclo[8,3,1,0^1,8,0^3,7] tetradecane. The stereochemistry of the new chiral centers were determined by ¹H NOE experiments.     

SRN1 Arylation of Some Heterocyclic Ketene Aminals with 2,4-Dinitrohalobenzenes

the anion of heterocyclic ketene aminals 1 - 4 reacted with 2, 4-dinitrohalobenzenes 5 to give the monoarylated products 6, 7, 9 and 11 by a S_RN1 mechanism. In some cases, the diarylated products 8 and 10 were also isolated.     

Useful Synthesis of Coumestans

A convenient synthesis of coumestans involving a combination of lithiation and Wittig reactions is described. Compounds 1a and 1b on reaction with n-butyllithium followed by treatment with diethyloxalate provide ketoesters 3a and 3b. Reaction of 3(a-b) with phosphorane generated from salt 4 gives 5(a-b) which on reaction with pyridine hydrochloride yield 7(a-b). DDQ oxidation of 7(a-b) gives coumestans 8(a-b).     

Synthesis of the Four Configurational Isomers of N-Benzoyl-2, 3, 6-Trtdeoxy-3-C-Methyl-3-Amino-L-Hexose from the (2S, 3R)-Diol Obtained from α-Methylcinnamaldehyde by Fermentation with Baker'S Yeast

Abstract

The erythro and threo chiral C₅ methyl ketones (4) and (5), prepared from the (2S, 3R)-methyl diel (1b), were converted into the phenylsulfenimines (6) and (7), which, in turn, on reaction with allyl-magnesiutn bromide, yielded after acid hydrolysis and benzoylation, the diastereoisomeric C₈-N-aminodiol derivatives (9) and (11), with threo stereochemistry relative to positions 4 and 5. Ozonolysis of (9) and (11) yielded the l-arabino and l-xylo 3-O-methyl branched aminodeoxysugar derivatives (13) and (15), respectively. Using diallylzinc as the reagent, the diastereoisomeric erythro products (8) and (10) were obtained. The latter materials gave the l-ribo-and l-lyxo-(lL-vancosamine) derivatives (12) and (14) upon oxonolysis. The ¹H and ¹³C NMR spectra of the four isomeric aminodeoxysugar derivatives (12)—(15) were discussed.     

REACTIONS OF DITHIOLETHIONES WITH N,N-DICHLOROAMIDES

Abstract

Dependent on the starting materials and the reaction conditions N,N-dichloroamides Cl₂N-X (X = COaryl, CO₂alkyl, SO₂aryl, SO₂N(alkyl)₂) react with dithiolethiones 1 and 5 to N-(dithiolyliden)amides 2, 6, S-(dithiolylidene)sulfimides 3, thionoxides 7 and dithiolones 4, 8. The mechanisms have been studied.     

Oxidation of Cyclic Hemiacetals into Diketones: Final Steps in the Conversion of a Triterpenoid Ring a into a Steroidal Enone by a New Short Route

As a part of our studies in the conversion of triterpenoids into steroids we have reported¹ that the Jones oxidation of some triterpenoid hemiacetals (1) gives acyloxy acids (2) instead of the desired 1,5-diketones (3). We now report² the shortest route yet for the reconstruction of a triterpenoid ring A ketone (4) into a steroidal enone (7) involving as key steps the exhaustive Baeyer-Villiger oxidation³ of triterpenoid ketones (4) into δ-lactones (5) and mild chromium(VI) oxidation of cyclic hemiacetals (1) into diketones (3).     

NOUVELLE SYNTHÈSE DE [1,2-A]BENZIMIDAZOLO-1,3,5,2-TRIAZAPHOSPHORINES ET DE [1,2-A]BENZIMIDAZOLO-1,3,5,2- TRIAZAPHOSPHORINE-2-THIONES

The condensation of N₁-benzimidazolyl amidines 1 with tris(dimethy- lamino)phosphine leads to the corresponding [1,2a]Benzimidazolo-1,3,5,2-triazaphosphorines 3 . The N₂-phosphoroamidine intermediates 2′ are isolated and yielded the corresponding cyclic compounds 4 upon heating. The oxidation by sulfur of the compounds 3 gives the thiooxide derivatives 4 .

The structure of these compounds is unambiguously confirmed by IR, ¹H, ³¹P, and ¹³C NMR spectroscopy and by MS for some products.     

Synthesis of 4-O-(α-L-Rhamnopyranosyl-D-Glucopyranuronic Acid

Abstract

Two approaches were used for the synthesis of 4-O-(α-l-rhamno-pyranosyl)-d-glucopyranuronic acid (1). Rhamnosylation of benzyl 6-O-allyl-2,3-di-O-benzyl-β-d-glucopyranoside (7), followed by deallylation, oxidation to uronic acid, and deblocking afforded 1. Alternatively, rhamnosylation of suitably protected d-glucuronic acid derivatives (25 and 26) gave the protected pseudoaldoBiouronic acid derivatives (19 and 30), which were deprotected. Rhamnosylations were performed in high stereoselectivity without neighbouring-group assistance using 2,3,4-tri-O-benzyl-1-O-trichloroacetimidoyl-α-l-rharnnopyranose (27) with tri-fluoromethanesulfonic acid catalysis.     

Solvolysis of 9-Bromo-ω-bromolongifolene/9-bromo-longifolene: Synthesis of Longi-β-Nozigiku Alcohol/Longicyclenyl Alcohol from Japanese Sugi/Hinoki Essential Oils

Longi-β-nozigiku alcohol 3/longicyclenyl alcohol 4 reported in Japanese sugi/hinoki essential oils, have been synthesized from longicyclene 2 using bromination as the key step. 9-Bromo-ω-bromo longifolene 5 (prepared from 2 by action of pyridine perbromide) is exposed to silver perchlorate in aqueous acetone to afford the ω-bromo-alcohol 7; refluxing 3. with Na-t-BuoH-THF gives the homoallylic alcohol 3. Solvolysis of 9-bromolongifolene 6 (prepared by bromination of 2 with NBS in CHCl₃ at reflux) with KOAc in ACOH at 75°/4 hr followed by hydrolysis furnishes longicyclenyl alcohol 4.     

Syntheses of Pseudo-α-D-Glucopyranose and Pseudo-β-L-Altropyranose From L-Arabinose

Abstract

Two optically active pseudo-hexopyranoses, pesudo-α-D-glucopyranose (1) and pseudo-β-L-altropyranose (2), were synthesized starting from L-arabinose. L-Arabinose was first converted to an acyclic aldehyde 9. The reaction of 9 with dimethyl malonate under basic conditions provided a tetra-hydroxylated cyclohexane-1,1-dicarboxylate 11 and a C-glycoside of β-L-arabinopyranose 12. From the compound 11, the desired two pseudo-sugars were synthesized by 1) thermal demethoxy-carbonylation, 2) LiAlH₄, reduction, 3) hydroboration of the resulting 1-hydroxymethyl-l-cyclohexene 14 followed by hydrogen peroxide treatment, and 4) removal of the protecting groups.     

Synthesis of 2-Aryl-1H-s-Triazolo[1, 5-a] Benzimidazoles

2-Aroylaminobenzimidazoles (2) have been converted into 1(2-benzimidazolyl)-5-aryl-1H-tetrazoles (4) by treatment with PCl₅ followed by azidation with NaN₃ in aqueous acetone solution. Pyrolysis of 4 in diphenylether yielded 2-aryl-1H-s-triazolo [1,5-a] benzimidazoles (6). The product of benzylation of 6a has been characterised. A reasonable pathway for the formation of 6 from 4 has been suggested.     

Synthesis of Methyl 1-Thio-L-Rhamnopyranoside-Derivatives

Abstract

Both anomers of methyl 1-thio-L-rhamnopyranosides were prepared through methylation of the corresponding isothiouronium salt. 2,3-0-Isopropylidene-, benzylidene-and the until now unknown diphenyl-methylene acetals were synthesized. Phase-transfer catalysed benzylation and LiA1H₄-AlCl₃-type hydrogenolysis of benzylidene acetals were used to obtain partially benzylated derivatives. Comparing the C NMR data of the synthesized compounds with those of their 0-glycoside analogues revealed that the 0→S exchanges at the anomeric centres caused drastic upfield shifts (～15 ppm) at C-1 and moderate downfield shifts at C-2 and C-5, as well. The chemical shift values of other carbons are not sensitive to the 0→S replacement.